The present invention relates to 4-(4-chlorophenyl)-1,2,3,6-tetrahydro-1-[4-(1H-1,2,4-triazol-1-yl)butyl]pyridine, of formula 
or one of its physiologically acceptable salts, pharmaceutical compositions thereof and their use in the production of medicines for use in human and/or veterinary therapy for the treatment of psychoses.
Schizophrenia comprises a heterogeneous group of disorders with various etiological and pathogenic mechanisms. The symptoms of the disease have been classified as positive and negative. The positive symptoms include delirium, hallucinations, paranoia and disorganized behavior and speech. The negative symptoms include loss of energy, speech defects, lack of initiative, loss of sociability and alteration of emotions.
Blocking of the D2 receptor of dopamine is considered to be the basic mechanism of action of the classical antipsychotics, such as haloperidol. However, the clinical efficacy of antagonists of the D2 receptor of dopamine has been shown to be limited, because although they are effective for treating the positive symptoms of the disease, they are not sufficiently effective for treatment of the negative manifestations and moreover they are associated with undesirable effects such as extrapyramidal effects and the development of tardive dyskinesias after prolonged administration.
The search for an xe2x80x9cidealxe2x80x9d antipsychotic that would be effective both for the positive and for the negative symptoms but without the undesirable effects of the classical neuroleptics has led to a new generation of antipsychotics known as atypical antipsychotics such as clozapine. However, clozapine has the problem of possible induction of agranulocytosis. Therefore its clinical use has been restricted to the treatment of schizophrenic patients resistant to other treatments, and in addition submitting the patients to regular blood tests for detecting the possible induction of agranulocytosis. These problems in the treatments currently available in human clinical practice were the stimulus for the search for new atypical antipsychotics, with experimental pharmacological activity similar to that of clozapine. Although this aim has been achieved in part, nevertheless there are no products that are genuinely effective against the negative manifestations of schizophrenia.
In recent years it has been demonstrated that the ligands of the sigma ("sgr") receptors have antipsychotic properties both in animal studies [Karbon et al., J. Pharmacol. Exp. Ther., 1993, 265, 866; Maj et al., Eur. J. Pharmacol., 1996, 315, 235; Akunne, Neuropharmacology, 1997, 36, 51] and in clinical trials [Snyder et al., J. Neuropsychiatry Clin. Neurosci., 1989, 1, 7; Frboes et al., Psychopharmacology, 1997, 132, 82] with a negligible incidence of extrapyramidal effects. In the sigma ("sgr") receptors, two subtypes have been identified and characterized pharmacologically: "sgr"1 and "sgr"2.
Compounds of the following general formula are described in our U.S. Pat. No. 5,731,331 and divisional patent application U.S. application Ser. No. 09/031,024, filed on Feb. 26, 1998. 
which have affinity for the a and 5HT1A receptors, and are claimed as medicines that can be used in the treatment of anxiety, psychoses, epilepsy, convulsion, amnesia, cerebrovascular diseases and senile dementia. The disclosures of the above-mentioned patent and application are incorporated herein by reference.
We have now found that the compound 4-(4-chlorophenyl)-1,2,3,6-tetrahydro-1-[4-(1H-1,2,4-triazol-1-yl)butyl]pyridine, as well as its physiologically acceptable salts, have great affinity for the "sgr" receptors, and especially for the "sgr"1 receptor. Moreover, their pharmacological properties indicate that they are atypical antipsychotics with particular properties with respect to the negative manifestations that are superior to the products developed up to now, and therefore these compounds are especially useful for the production of medicines, in human and/or veterinary therapy, for the treatment of psychoses.
The present invention relates to 4-(4-chlorophenyl)-1,2,3,6-tetrahydro-1-[4-(1H-1,2,4-triazol-1-yl)butyl]pyridine, of formula 
or one of its physiologically acceptable salts, pharmaceutical compositions thereof and their use in the production of medicines that can be used in human and/or veterinary therapy for the treatment of psychoses.
Physiologically acceptable salts of the compound 4-(4-chlorophenyl)-1,2,3,6-tetrahydro-1-[4-(1H-1,2,4-triazol-1-yl)butyl]pyridine refer both to the salts formed with inorganic acids and with organic acids, in particular to the salts of hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, lactic, masonic, succinic, glutaric, fumaric, malic, tartaric, citric, ascorbic, maleic, benzoic, phenylacetic, cinnamic, and salicylic acids, and alkyl, cycloalkyl or arylsulfonic acids, such as methanesulfonic or p-toluenesulfonic acids.
The use of 4-(4-chlorophenyl)-1,2,3,6-tetrahydro-1-[4-(1H-1,2,4-triazol-1-yl)butyl]pyridine, or one of its physiologically acceptable salts, for the treatment of psychoses refers to their use as antipsychotics in clinical practice.